December 2 Friday
Objectives for Cardiovascular Course 1
10-11:00am HSEB 1730 CHF, CMP, Myocarditis Dr. Clayton 5
December 6 Tuesday
11-12:00am HSEB 1730 Valvular Disease and Endocarditis Dr. Urie 11
December 8 Thursday
8-9:00am HSEB 17370 Mandatory Olympus & PACS Training Dr. Clayton/Bown
11-12:00pm HSEB 1730 Atherosclerosis and Hypertension Dr. Urie 18
1-3:00pm HSEB 4300 Pathology Laboratory – Clayton/Staff 23
Casepath Notes 24
December 12 Monday
9-10:00am HSEB 1730 Ischemic Heart Disease Dr. Urie 38
10-11:00am HSEB 1730 Miscellaneous Cardiac Diseases Dr. Urie 45
December 15 Thursday
10-12:00pm HSEB 4300 Pathology Laboratory Clayton/Staff 53
Congenital Hearts and Case Presentations
December 16 Friday
Be sure to check the web for changes that may have occurred after printing
Pathology 6020 – Year 2005
Paul M. Urie, M.D., Ph.D.
Frederic Clayton, M.D.
Suggested Reading and Study:
Webpath cardiovascular sections (Organ System and Lab Exercises)
Pathologic Basis of Disease, Ch 11-12, pp. 512-618
A. Heart Failure
1. Outline the pathophysiologic mechanisms and cause of congestive
2. Compare and contrast:
"left-sided" and "right-sided" congestive heart failure
cor pulmonale and cor bovinum
cardiac tamponade and constrictive pericarditis
In terms of: defining features
pathogenesis and most frequent causes
3. Compare the following congenital diseases of the great vessels:
coarctation of aorta
patent ductus arteriosus
transposition of the great arteries
In terms of:
major morphologic features
major alterations in blood flow
effect on arterial blood oxygenation
4. List the morphologic defects and abnormal blood flow patterns in:
Tetralogy of Fallot
Transposition of great vessels
5. Describe forms of symptomatic congenital heart disease most
commonly encountered in each of the following age groups:
birth to two weeks
1 month to 1 year
10 years to 30 years
6. Describe forms of cyanotic congenital heart disease with and
without pulmonary hypertension.
7. Define three syndromes in which congenital heart disease is
associated with multiple non-heart congenital anomalies.
8. Describe forms of congenital heart disease manifest in the
neonatal period in which adequate systemic perfusion is
dependent upon patency of the ductus arteriosus.
B. Rheumatic Heart Disease: Compare acute and chronic stages of
rheumatic heart disease:
complications including extracardiac lesions
symptoms, signs and laboratory abnormalities
C. Chronic non-effective Valvular Disease: Define non-bacterial thrombotic
endocarditis, know its pathogenesis, significance and complications.
D. Infective Valvular Disease:Discuss infective endocarditis in the context of:
epidemiology, citing at least four common predisposing factors
organisms that are responsible
complications and prognosis
E. Miscellaneous Valvular Disease & Endocarditis
1. Outline possible etiology and pathophysiology for:
aortic stenosis and insufficiency
mitral stenosis and insufficiency
F. Myocarditis and Cardiomyopathy
1. Compare myocarditis with cardiomyopathy in terms of causes,
morphology, and diagnostic features.
2. Outline the classification of cardiomyopathies.
G. Ischemic Heart Disease
1. Describe pathogenetic sequences by which coronary
congestive heart failure
In terms of:
H. Myocardial Infarction
1. Given a histologic section of infarcted myocardium, date the infarct
from the microscopic appearance.
2. List the tissue and serum enzyme changes in myocardial infarction,
indicating when they appear and disappear.
3. Indicate the factors that determine the location and size of a
4. Describe the risk factors for myocardial infarction and how they can
I. Pericardial Disease
1. Classify pericarditis according to causes.
2. Describe clinical findings with pericarditis and pericardial effusion.
systemic lupus erythematosus
giant cell arteritis
In terms of:
size and type of vessels involved, if any
organs commonly involved
relative frequency and prognosis
2. Describe syphilitic aortitis in terms of:
gross and microscopic appearance
distribution of the lesions
usual clinical presentation
K. Arteriosclerosis - Clinical Aspects
1. Describe the gross and microscopic appearances of the lesions of
atherosclerosis at different stages of development.
2. Discuss at least four predisposing factors in the development of
atherosclerosis in terms of evidence indicating the importance of
3. List the usual clinical manifestations of at least four common major
complications of atherosclerosis.
4. Compare the effects of aortic, coronary and cerebral
1. Define and use in proper context:
2. Compare thoracic and aortic aneurysms of the aorta by:
M. Venous Diseases
1. Define varicose veins indicating predisposing factors,
2. Describe causes and consequences of venous thrombosis and
N. Cardiac Tumors - Compare and contrast the following neoplasms:
angiosarcoma metastatic carcinoma
In terms of:
frequency location consequences
Pathology 6020 - Year 05
Frederic Clayton, MD
Dec. 2, Friday
CONGESTIVE HEART FAILURE, CARDIOMYOPATHY AND MYOCARDITIS
I. Congestive heart failure
A. Definition - the pathophysiologic state resulting from impaired
cardiac function rendering the heart unable to maintain an output
sufficient for the metabolic requirements of the tissues and organs
of the body.
CHF occurs either because of a decreased myocardial capacity to
contract or because an increased pressure-stroke-volume load
imposed on the heart.
Systolic dysfunction - deterioration of myocardial contractility
Diastolic dysfunction - insufficient expansion to accommodate
B. Mechanisms of compensation
2. Frank-Starling mechanism - increased end-diastolic volume
causes increased stroke volume (more venous return
increases blood flow)
3. Myocardial hypertrophy - not hyperplasia
4. Catecholamines by the adrenal medulla – increase
5. Renin-angiotensin-aldosterone system increases blood
6. Adrenergic-mediated redistribution of blood flow
7. Increased oxygen extract from hemoglobin
C. Left-sided failure
1. Usual causes
a. Ischemic heart disease
c. Aortic and mitral valve disease
d. Myocardial disease
2. Systemic effects
a. Lungs - pulmonary edema and congestion
dyspnea - breathlessness
orthopnea - dyspnea lying down (increased venous
paroxysmal nocturnal dyspnea - extreme dyspnea in
bed, bordering on suffocation
cough - frothy, blood-tinged sputum
b. Kidneys - reduction in renal perfusion causes
ischemic tubular necrosis and prerenal azotemia
c. Brain - cerebral hypoxia - irritability, loss of attention
span, restlessness, stupor and coma
D. Right-sided heart failure
a. Pure - cor pulmonale, tricuspid or pulmonic valve
b. Consequence of left-sided failure - mitral stenosis
and left-to-right shunts
c. Other - myocarditis, cardiomyopathy, constrictive
2. Systemic effects
a. Liver - chronic passive congestion, central
hemorrhagic necrosis, cardiac sclerosis
b. Spleen - congestive splenomegaly
c. Kidneys - congestion and hypoxia
d. Subcutaneous tissue - peripheral edema, anasarca
e. Pleural spaces - effusions
f. Brain - venous congestion and hypoxia
g. Portal system - ascites
A. Clinical significance
Frequency of the disease is unclear – symptoms are nonspecific
so diagnosis is often missed. Most cases are probably of viral
origin. Symptoms and signs depend on the etiology and severity -
vary from sudden congestive heart failure to fatigue, dyspnea,
palpitations and fever. ECG may show diffuse ST-T segment
changes and chest x-ray may show cardiac dilatation.
B. Classification by etiology
1. Viral - Coxsackie A and B, ECHO, influenza, poliomyelitis,
viral hepatitis, EBV, and cytomegalovirus
2. Chlamydia - C. psittaci
3. Rickettsia - R. typhi (typhus fever) and R. tsutsugamushi
4. Bacteria - diphtheria, salmonella, TB, strep, meningococcus,
5. Fungal and protozoa - trypanosoma (Chagas' disease),
candida, toxoplasmosis, aspergillus, Blastomyces,
cryptococci, and coccidiomycosis
6. Metazoa - echinococcus, trichinella
7. Hypersensitivity - RHD, SLE, systemic sclerosis, drugs
8. Physical agents - radiation, heat stroke
9. Idiopathic - giant cell myocarditis
C. General morphology
1. Gross - cardiac dilatation, flabby myocardium with pale
patches of yellow-gray and hemorrhage on the cut surface
2. Microscopic - interstitial inflammatory infiltrate with focal
myocyte necrosis and focal fibrosis. Type of infiltrate is
suggestive of the etiology.
mononuclear - most types including idiopathic
neutrophils - bacteria
eosinophils - hypersensitivity, protozoa, Metazoa
D. Specific entities
1. Viral - most common etiology of myocarditis and is difficult to
diagnose - rising viral titers and endomyocardial biopsy viral
cultures. EM has not been productive. May develop into
2. Bacteria - direct heart invasion with suppurative response.
Diphtheria produces an exotoxin which causes myocyte necrosis.
Toxoplasmosis (infected soil passed to pets and man)
affects young and immunocompromised host (heart
Trypanosoma (Chagas' disease) - passed in the feces of the
Reduviidae bugs and penetrate broken skin or intact
mucous membranes. Parasitization of myocytes with
inflammatory infiltrate and the formation of pseudocysts.
Fibrosis and congestive heart failure may be seen.
4. Hypersensitivity reactions - numerous drugs and toxins
5. Giant cell myocarditis - myocyte necrosis with multinucleate
giant cells, lymphocytes, plasma cells, macrophages, and
neutrophils. Often fulminant with rapid progression to death.
III. Cardiomyopathy - heart muscle disease of unknown etiology
A. Dilated or congestive cardiomyopathy
Gross - increased weight, dilatation of ventricle, mild
endocardial thickening, normal coronary arteries and valves
Microscopic - myocyte hypertrophy with large, bizarre
nuclei; myofibrillar loss, and interstitial fibrosis
selenium deficiency (Keshan's disease)
3. Clinical significance:
atrial fibrillation with thrombosis and embolism
B. Hypertrophic cardiomyopathy (IHSS, ASH)
a. Disproportional hypertrophy of ventricular septum
b. Myofiber disarray (100%)
c. Reduction in the volume of ventricular cavities (90%)
d. Endocardial thickening in the left ventricular outflow
e. Mitral valve thickening (75%)
f. Dilated atria (100%)
g. Abnormal intramural coronary arteries (50%)
2. Etiology - genetic – usually autosomal dominant,
occasionally sporadic. Due to mutations of any of several
3. Clinical significance
Symptoms - dizziness, syncope, LV failure, arrhythmias,
reduction of cardiac output by obstruction and reduced LV
volume, reduced LV compliance, sudden death rate 2-6%
C. Restrictive/infiltrative/obliterative cardiomyopathy - restrict cardiac
1. Endomyocardial fibrosis – children and young adults in
Africa with fibrosis of one or both ventricles. Subendocardial
scarring involving inner third of myocardium. Unknown
etiology, might be due to high food serotonin levels.
2. Loeffler's endocarditis - endomyocardial fibrosis,
eosinophilic leukocytosis, myocardial necrosis and
eosinophilic infiltrate, fibrosis, heart failure.
3. Endocardial fibroelastosis - focal or diffuse fibroelastic
thickening of the endocardium without myocardial necrosis.
Unknown etiology - hereditary, hypoxic, pressure overload,
lymphatic obstruction, or viral.
4. Infiltrative cardiomyopathies such as amyloidosis and
IV. Specific heart muscle disease
1. Toxic - alcohol, cobalt, catecholamines, Cocaine,
2. Metabolic - hemochromatosis, nutritional deficiency, thyroid
3. Neuromuscular disease - Friedreich’s ataxia, muscular
4. Storage disease - glycogen, Fabry's disease
5. Infiltrative - sarcoidosis
B. Sarcoidosis - noncaseating granulomata replacing heart muscle
and healing with fibrosis (20-30% heart involvement).
C. Hemochromatosis - myocardium and conduction system with heart
failure and arrhythmias either primary or secondary.
D. Rheumatoid heart disease - rheumatoid nodules within arteries,
valves, myocardium, and pericardium.
Pathology 6020 - Year 2005
Paul M. Urie, MD, PhD
December 6, Tuesday
VALVULAR HEART DISEASE AND ENDOCARDITIS
I. Definitions and classification
A. Stenosis - failure of a valve to open completely preventing forward
Regurgitation (insufficiency) - failure of a valve to close completely
allowing reverse flow
B. Classification based on etiology
1. Aortic stenosis
a. Post-inflammatory scarring - RHD, infective
b. Senile calcific aortic stenosis
c. Calcification of congenitally deformed valve
2. Aortic regurgitation
a. Post-inflammatory scarring
b. Aortic disease
1. Syphilitic aortitis
2. Ankylosing spondylitis
3. Rheumatoid arthritis
4. Marfan's syndrome
3. Mitral stenosis – post-inflammatory scarring
4. Mitral regurgitation
a. Leaflet abnormalities
1. Post-inflammatory scarring or infective
2. Floppy mitral valve syndrome
b. Tensor apparatus abnormalities
1. Rupture or dysfunction of papillary muscle
2. Rupture of chordae tendineae
c. LV abnormalities
1. LV dilatation
2. Calcification of mitral ring
II. Rheumatic fever and rheumatic heart disease
A. Definition - systemic disease characterized by migratory
polyarthritis of the large joints, carditis, erythema marginatum of
the skin, subcutaneous nodules, and Sydenham's chorea - a
neurologic disorder with involuntary purposeless rapid movements.
B. Revised Jones' criteria for the diagnosis of rheumatic fever
1. Major criteria
d. Erythema marginatum
e. Subcutaneous nodules
2. Minor criteria
1. Previous rheumatic fever or RHD
1. Acute phase reactions - ESR, C-reactive
2. Prolonged P-R interval on ECG
3. Supporting evidence of strep infection
a. Increased titer of antistreptolysin O (ASO) and other
b. Positive throat culture for group A beta-hemolytic
streptococcus weeks prior
c. Recent scarlet fever
1. Probability of RF is strongly correlated with severity and
duration or the pharyngitis and the magnitude of the immune
2. Risk factors include crowding, cold climates, poor living
conditions, and inadequate medical care.
3. Mortality rate in 1940 20.6/100,000 to 2.2/100,000 in 1982
1. Heart valve glycoproteins cross-react with hyaluronate
capsule of streptococci.
2. Cross reactivity is present between cardiac muscle and
strep antigens - streptococcal cell wall M proteins.
3. Cytotoxic T lymphocytes sensitized to strep antigens lyse
4. Immunoglobulins and complement are fixed to sarcolemmal
sheaths of cardiac myocytes and are found in Aschoff
1. Aschoff body - most distinctive feature found in interstitial
connective tissue either perivascular, subendocardial, or
rarely subepicardium and valves
a. Exudative lesion - fibrinoid necrosis
b. Classic proliferative cellular lesion - fibrinoid
necrosis, cardiac histiocytes (Anitschkow cell) and
plasma cells, lymphocytes, neutrophils and mast cells
c. Progressive fibrosis or healed lesion
2. Cardiac - 50-75% in children 2-16 years and 35% in adults
a. Pericarditis - diffuse fibrinous inflammatory reaction
b. Myocarditis - interstitial connective tissue
mitral valve 40-50%
aortic valve 15-20%
mitral and aortic valves 35-40%
mitral, aortic, tricuspid 2-3%
friable vegetations (verrucae) along lines of closure of
leaflets - fibrinoid necrosis with leukocyte infiltrate
leading to fibrous scarring and calcifications
3. Other sites - joints, skin, arteries, lung and pleura
III. Infective endocarditis
A. Definition - infection of heart valves, A-V shunts, coarctations of
aorta, mural endocardium and prosthetic heart valves
a. Causative agent - Staphylococcus aureus and
streptococci are most frequent, Pseudomonas in
some with intravenous drug use as a risk; others
include: gonococci and coliforms; Candida and
Aspergillus in immunocompromised patients.
b. Usually normal hearts; also previous cardiac surgery,
immunodeficiency, or immunosuppression.
c. Metastatic foci of infection common
d. Symptoms - high fever, shaking chills, weakness,
e. Mortality can reach 70% and often results in
permanent valve damage
f. Associated with chronic alcoholism and drug
a. Causative agent - Streptococcus viridans group and
b. Most hearts have underlying cardiac disease
c. Metastatic foci of infection rare
d. Symptoms - progressive weakness, weight loss,
fever, anemia, night sweats, splenomegaly
e. Mortality 10-40%
1. Occurs at sites of alteration of blood flow - jet effect causing
endothelial injury and low pressure sinks favoring deposition
of fibrin and clumps of organisms
2. Bacteremia may follow dental, urological manipulations, IV
drug abuse or vascular catheters
3. Agglutinating antibodies develop causing clumping of
organisms and allowing them to precipitate on valve.
4. Pathogenesis of acute bacterial endocarditis is less clear
1. Sites of involvement - mitral valve 25-30%, aortic valve 25-
35%, tricuspid valve 10%, valve prosthesis 10%, congenital
2. Friable, bulky vegetations containing platelets, red cells,
fibrin, inflammatory cells, bacteria with neovascularization at
the base and occasional fibrosis and calcification
3. Cardiac complications
a. Coronary artery embolization
b. Abscess formation
c. Erosion or perforation of valve or chordae tendineae
4. Non-cardiac complications
a. Septic emboli producing splinter hemorrhages of
nails, Osler nodes and Janeway lesions on skin;
emboli lodged in arteries may produce mycotic
b. Immune complex deposits - glomerular lesions and
IV. Nonbacterial thrombotic endocarditis - marantic endocarditis
A. Morphology - sterile, small (1-5 mm) vegetations containing fibrin
and platelets along the line of closure of the aortic or mitral valve
B. Clinical significance - predisposing conditions include metastatic
malignancy, hypercoagulable states, chronic debilitating diseases, and
endocardial trauma. May become secondarily infected and may be a
source of arterial emboli.
V. Nonbacterial verrucous endocarditis (Libman-Sacks disease)
Mitral and tricuspid valvulitis with active systemic lupus erythematosus
with mucoid pooling, fibrinoid necrosis, and fibrosis within the connective
tissue of the valves.
VI. Calcific aortic valve stenosis
A. Pathogenesis and morphology - usually follows infective
endocarditis or rheumatic fever but occurs more often in congenital
bicuspid valve or in normal valves with advancing age. Fibrosis
and calcification obliterate the sinuses of Valsalva and valve
B. Clinical significance – critical obstruction is a reduction of valve
area by 2/3 or 50 mmHg pressure gradient (<1 cm2
Results in pressure overload, LV hypertrophy and heart failure.
Increased incidence of sudden death.
VII. Calcification of mitral valve annulus
Irregular stony hard beading (2-5 mm in thickness) in the mitral valve
annulus; often associated with ischemic heart disease.
May narrow lumen and impinge on the conduction system. Elderly
individuals, especially women.
VIII. Mitral valve prolapse
A. Morphology - excessively large leaflets or excessively long
chordae tendineae; myxomatous change within the valve leaflet
usually affects posterior leaflet.
B. Etiology - unknown - Marfan's syndrome, hereditary disorders of
C. Clinical significance - 5-7% of general population most commonly
young women; complications include regurgitation, arrhythmias,
susceptibility of infective endocarditis and psychiatric
IX. Complications of artificial valves
B. Anticoagulant-related hemorrhage
C. Infective endocarditis
D. Structural or biologic deterioration (bioprosthesis)
E. Nonstructural dysfunction - tissue entrapment, paravalvular leaks,
X. Phentermine (Fastin) and Fenfluramine (Pondimin) valvular disease.
A. Morphology similar to carcinoid valvular disease with fibrous
plaques on valve leaflets, primarily the mitral valve resulting in
B. Treatment is surgical repair or replacement of the valve.
Pathology 6020 - Year 2005
Paul M. Urie, MD, PhD
Dec. 8, Friday
ATHEROSCLEROSIS AND HYPERTENSION
I. Normal Vessels
A. Types of arteries
Large or elastic
Medium or muscular
B. Layers of arteries
II. Arteriosclerosis - hardening of the arteries
Mönckeberg’s medial calcific sclerosis
1. Risk factors
Diet and hyperlipidemia
High carbohydrate intake
a. Fatty streak
b. Atheromatous plaque - fibrous plaque, fibrolipid and
Cellular component - smooth muscle, macrophages,
Connective tissue extracellular matrix component
Intracellular and extracellular lipid component
c. Complicated lesion
1. dystrophic calcification within media or plaque
2. ulceration with rupture and cholesterol emboli
3. superimposed thrombosis with vascular
4. hemorrhage into the plaque
5. atrophy of media and loss of elastic tissue with
3. Theories of pathogenesis:
a. Chronic endothelial cell injury, increased
endothelial permeability, endothelial
b. Monocyte emigration in the intima with
accumulation of oxidized LDL.
c. Smooth muscle cell proliferation and
extracellular matrix deposition with smooth
muscle cell lipid accumulation.
d. Platelets adhere to damaged endothelium with
organization of thrombi.
a. Uniform laminar shear stress stimulus up-
regulates the expression of a subset of
“atheroprotective genes” in endothelial cells.
b. Locally protective in “lesion-protected areas”
to offset effects of systemic risk factors.
4. Clinical significance
a. narrowing of the vascular lumen causing
b. sudden occlusion of the lumen by thrombosis
or hemorrhage producing infraction
c. site of thrombosis and embolism
d. weakening of the wall of the vessel followed by
aneurysm or rupture
B. Mönckeberg’s arteriosclerosis
Basic lesion - ringlike calcification within the media of medium-
sized to small muscular arteries in individuals over 50 years of age.
Bone and bone marrow might be seen in the calcified media.
Lesions do not produce narrowing or occlusion of the vascular
Site of involvement - femoral, tibial, radial and ulnar arteries
Pathogenesis - unknown but related to prolonged vasotonic influence
A. Hyaline arteriolosclerosis
1. Morphology - homogeneous pink, hyaline thickening of the
walls of arterioles with loss of underlying structure and
narrowing of the lumen. Lesions are related to diabetes and
hypertension and may reflect leakage of plasma proteins
across vascular endothelium. Hyaline consists of collagen
and precipitated plasma proteins.
2. Clinical significance - associated with benign hypertension
and diabetes mellitus.
B. Hyperplastic arteriolosclerosis
1. Morphology - concentric, laminated, onionskin thickening of
the walls of arterioles with proliferation of smooth muscle
cells and layer of collagen narrowing of the lumen frequently
accompanied by deposits of fibrin and acute necrosis.
2. Clinical significance - associated with malignant or
accelerated phase hypertension.
3. Pathogenesis - vasoconstriction and increased blood
pressure causes endothelial injury, platelet thrombosis,
intravascular coagulation and vessel necrosis
IV. Hypertensive heart disease
A. Definition - left ventricular hypertrophy, usually concentric in the
absence of other cardiovascular pathology and a history of
Gross - concentric hypertrophy with left ventricular wall thickness
greater than 2.0 cm and total weight of heart greater than 500 gm;
decompensation of cardiac function produces dilatation of the left
Microscopic - increase in myofiber volume and mean diameter;
nuclei are enlarged, hyperchromatic and rectangular and have
bizarre shapes; interstitial fibrosis is present; arterioles show wall
Hypertension places pressure overload on the left ventricle and
causes vascular disease which increases peripheral vascular
resistance. The heart must hypertrophy to maintain a normal
cardiac output in the face of increased vascular resistance.
Hypertrophy with left ventricular wall thickening increases
myocardial oxygen demand. Eventual hypoxia of the cardiac
myocytes may induce decompensation and dilatation.
V. Cor Pulmonale (pulmonary hypertensive heart disease)
A. Definition - right ventricular hypertrophy and dilatation in response
to pulmonary hypertension not secondary to left heart failure or
congenital heart disease.
B. Acute - right ventricular dilatation following massive pulmonary
C. Chronic - right ventricular hypertrophy
1. Diseases of the Lungs
a. Chronic obstructive pulmonary disease
b. Diffuse pulmonary interstitial fibrosis
c. Extensive persistent atelectasis
d. Cystic fibrosis
e. Idiopathic - primary pulmonary hypertension
2. Diseases of pulmonary vessels
a. Pulmonary embolism
b. Primary pulmonary vascular sclerosis
c. Diffuse pulmonary arteritis
d. Drug, toxin, or radiation induced vascular sclerosis
e. Extensive pulmonary tumor micrometastases
3. Disorders affecting chest movement
b. Neuromuscular dystrophies
c. Marked obesity
4. Disorders inducing pulmonary arteriolar constriction
a. metabolic acidosis
1. Chronic altitude sickness
2. Obstruction to major airways
3. Idiopathic alveolar hypoventilation
Access labs at: www.path.utah.edu/class.htm
Cardiovascular Pathology Cases
Laboratory I - Thursday 12/8/05 1:00-3:00pm
Laboratory II - Thursday 12/15/04 10:00-12:00noon
Goals and Objectives:
Following the participation in lab sessions one and two the student will be able to:
1. Use the electronic medical record and/or computer to gather data on patients
2. Use the library electronic reference system to research data on diseases, therapies and
3. Understand the basic pathology, presentation, and treatment of cardiac disorders including:
b. Myocardial infarction
d. Cor Pulmonale
f. Sudden death
g. Valve replacements
4. Understand the basic pathology, presentation, and treatment of vascular disorders
a. Polyarteritis nodosa
b. Diabetic ischemic vasculopathy
5. Compile data on a patient and present it in the form of a Clinical Pathological Correlation.
Cardiovascular Casepath Notes
1. What is your differential diagnosis?
2. Why is this patient at risk for peripheral vascular disease?
1. What was the organism recovered from the wound?
2. Why is this patient having problems with recurrent infections?
3. Review the white cell count trends, what does this tell you about the infection?
1. Is the graft patent?
2. How do the native vessels appear?
3. What do you think about the graft cultures?
4. A CXR and EKG were performed on 8-31 prior to surgery. Are there any signs of cardiac
1. What do the premortem labs suggest?
2. What was the cause of her sudden death?
1. Discuss the diagnosis and management of Insulin dependent Diabetes Mellitus.
2. Discuss the mechanism of accelerated atherosclerosis including glycosylation of proteins
3. What are the incidence of amputations and peripheral vascular disease in DM?
4. Describe the increased risk of infection in DM.
5. What is the treatment of an infected graft?
6. What populations are at increased risk for DM in the U.S.?
7. What are the EKG findings in Myocardial Infarction?
1. What is your differential diagnosis?
2. What tests would you want to get?
3. What does an elevated sedimentation rate mean?
1. What is polyarteritis nodosa?
2. What additional risks does Factor V Leiden impose on this patient?
3. Review the EKG from this admission; are there any signs of cardiac ischemia?
4. An x-ray of the foot was performed to rule out osteomyelitis of the great toe, do you see any
1. What do these CBC findings have to do with his underlying vasculitis?
2. What changes are seen on CXR?
1. Are the autopsy findings consistent with polyarteritis nodosa?
2. What vessels are involved in this disorder?
3. What other vasculitides may present like this patient?
1. Describe polyarteritis nodosa, its diagnosis and treatment.
2. Is atherosclerosis associated with vascular damage?
3. How does Factor V Leiden affect atherosclerosis?
4. Describe the etiology of ischemic infarcts of the tissues in this case
5. How does immunosuppression increase the risk of infection?
1. What is your differential diagnosis?
2. How might the diagnosis of the lung biopsy have added to his current situation?
1. The patient had an aortogram on 10-18-03. How do his vessels look?
2. A CT scan with contrast performed on this admission is shown here. Are there any signs of
leakage in his AAA?
1. Review the EKGs below. What changes occurred in the heart since the last admission?
1. What was the cause of death?
2. What underlying causes of amyloidosis should be looked for at autopsy?
3. Is the aneurism related to the amyloid?
1. What are the etiologies of amyloidosis and how does amyloid present?
2. How does amyloid affect the heart and vessels?
3. What is the relation of bundle branch block with amyloid?
4. How do you diagnose abdominal aortic aneurism and what is the treatment?
1. What are the cardiac causes of shortness of breath?
2. How does lung disease affect the heart?
3. Review the admission laboratory results how did these help rule out the possibility of a
4. What do you see on his EKG?
5. What is your differential diagnosis?
1. Look at the patient’s O2 trends to get an idea of his lung function and how treatment with
2. What effect does oxygenation have on the heart?
1. What is this heart disease called?
2. What is the cause of death?
3. What is the significance of the patent foramen ovale?
1. What are the effects of lung disease on the heart?
2. How is the diagnosis of cor pulmonale made?
3. How do you diagnosis and manage right heart failure?
4. What is a patent foramen ovale, why does it occur in cor pulmonale and what risk does it
impose on the patient?
1. What is your differential diagnosis?
2. What is the extent of damage?
1. What are the patient's risk factors for coronary artery disease? What should his children be
2. Review the EKG, what abnormalities do you see? What is a bundle branch block?
3. Are there any abnormalities on CXR?
1. What is an intra-aortic balloon pump and how does it increase the cardiac output?
2. Review the chest films following balloon placement. What do you see?
3. What is the rhythm on the EKG?
1. The Admission H&P of 6-22-03 reveals the concern for epigastric pain. What could be
2. What does the troponin tell you?
3. Review the EKG from this admission, are there any changes?
4. Review the CT scan performed on 6-23-03, what do you see?
5. What could be the cause of death?
1. Explain the diagnosis and treatment of acute myocardial infarction.
2. What are the risk factors for acute myocardial infarction?
3. What are the risks for cardiac rupture (consider timing and location of infarct)?
4. Discuss congestive heart failure following infarction.
1. What do you note in the iliac artery runoff?
2. What do you see on the renal artery injections?
1. Review the labs on admission. What is her PaO2?
2. Review the EKG. Do you see any abnormalities?
3. Review her Chest X-ray on admission. Is the heart size normal? How do the lungs look?
1. What is the outlook for this patient?
2. What risk factors did this patient have for developing a deep venous thrombosis?
3. What serious sequela of DVT is she at risk for?
1. What is going on in her heart?
2. Is this acute or chronic?
3. What is a possible cause of death?
1. What is the diagnosis and treatment for renal artery stenosis?
2. How does renal artery stenosis cause hypertension?
3. Describe the development of left ventricular hypertrophy in hypertension.
4. What are the causes of sudden cardiac death?
1. Review the patient’s pre-operative labs. Does there appear to be any contraindication to
2. Review the pre-operative EKG. What are the findings?
3. Why does this patient have LVH?
4. Review her pre-operative Chest X-Ray 6-4-02. Are there any abnormalities?
1. Review the post-operative Chest X-Ray 6-5-03. What changes do you see?
2. Why might an aortic valve replacement affect the functioning of the myocardium?
1. What does the post operative blood gas tell you about her heart function?
1. What abnormalities do you see?
1. What are the attachments of the RVAD and the coronary grafts?
2. What are the microscopic findings in the heart?
3. What is the cause of death?
1. Describe the diagnosis and treatment of congenital bicuspid valve.
2. Describe aortic stenosis and its effects on the heart.
3. Is myocardial ischemia and infarction a risk of surgery?
4. Describe how the right ventricular assist device and aortic balloon pump help support a
1. What is your differential diagnosis?
2. Review the chest film from 4-4-03 on admission. Are there any abnormalities?
3. Review the labs from 4-4-03. Are there any clues to his illness
1. Should there have been follow up to the frozen section report of the mediastinal biopsy?
2. What is your differential diagnosis now?
1. What is the rhythm on the EKG?
2. What are the findings on the CT of the head?
1. What is your diagnosis now?
1. What is the diagnosis and treatment of endocarditis?
2. What are the etiologies of endocarditis?
3. What is the difference between marantic and infectious endocarditis?
4. Describe Trousseau Syndrome in adenocarcinoma.
Pathology 6020 - Year 2005
Paul Urie, M.D., Ph.D.
Dec. 12, Monday
ISCHEMIC HEART DISEASE AND CARDIAC ENZYMES
Reading: Robins Pathologic Basis of Disease 7th
edition: pages 571-587; or in
edition pages 550-564.
Accounts for 80% of deaths caused by heart disease or 30% of the total
mortality in the United States. Mortality from IHD in the U.S. has
decreased by 50% since 1963.
IHD is caused by an imbalance between the myocardial blood flow and
the metabolic demand of the myocardium.
A. Reduced coronary blood flow
Reduction in coronary blood flow is due to progressive stenosis by
atherosclerosis in 90% of patients with IHD. Other etiologic factors
are: vasospasm, thrombosis, or circulatory changes leading to
Basic principle - coronary artery perfusion depends on the
pressure differential between the ostia (aortic diastolic pressure)
and coronary sinus (right atrial pressure). Blood flow is reduced
during systole because of Venturi effects at the coronary orifices
and compression of intramuscular arteries during ventricular
Factors reducing coronary blood flow
1. Decreased aortic diastolic pressure
2. Increased intraventricular pressure and myocardial
3. Coronary artery stenosis - transient or fixed
a. Fixed coronary stenosis
b. Acute plaque change
-Not dependent on percent of fixed stenosis
-Role of Inflammation and C-reactive protein
c. Coronary artery thrombosis
4. Aortic valve stenosis and regurgitation
5. Increased right atrial pressure
Coronary artery distribution patterns and frequency of stenosis
anterior wall left ventricle, apex
descending, anterior IV septum
posterior wall left ventricle,
posterior IV septum
lateral wall left ventricle
Intramyocardial collateral vessels are present in all hearts with
pressure gradients permitting flow despite occlusion of major
The cross-sectional area of the coronary artery lumen must be
reduced by more than 75 percent to significantly affect perfusion.
Coronary atherosclerosis is segmental, and usually involves the
proximal 2 cm of arteries (epicardial).
B. Increased myocardial oxygen demand
Hypermetabolism - exercise
C. Availability of oxygen in the blood
Right to left shunting of blood
III. Patterns of ischemic heart disease
A. Angina pectoris - a symptom complex of IHD characterized by
paroxysmal attacks of chest pain, usually substernal or precordial,
caused by myocardial ischemia that falls short of inducing
1. Stable angina (typical) - paroxysms of pain related to
exertion and relieved by rest or vasodilator, subendocardial
ischemia. Chronic, fixed atheromatous plaques that are
2. Variant or Prinzmetal's angina - angina that classically
occurs at rest and is caused by reversible spasm of the
3. Unstable angina - prolonged pain, pain at rest in a person
with stable angina, or worsening of pain in stable angina.
Abrupt disruption, fissure, or thrombosis that is
nonocclusive. This may be the prodrome to MI.
B. Sudden cardiac death - Unexpected death from cardiac causes
usually within one hour after cardiac symptoms or without the onset
of symptoms. Most common is plaque disruption and acute
thrombus, platelet aggregates or thromboemboli. It strikes
300,000-400,000 persons annually. (Also includes other cardiac
disorders (10-20%): congenital abnormalities, aortic stenosis,
MVP, myocarditis, cardiomyopathies, pulmonary hypertension,
Death is due to ventricular electrical instability (arrhythmia).
C. Myocardial infarction
1.5 million people in US affected annually. 30% die - half in the first
hour. 250,000 people/year die before reaching hospital. Women
are relatively protected during reproductive years, but estrogen
replacement does not slow atherosclerosis after menopause.
Transmural infarct - usually involves the LV or in 15-30% it
may involve septum with extension into the RV. Isolated
infarcts of RV and right atrium are extremely rare. Infarct is
within area fed by one coronary vessel.
Pathogenesis of transmural infarcts (most common type of
a. Occlusive coronary thrombus overlying an ulcerated
or fissured stenotic plaque causes 90% of transmural
b. Vasospasm with or without coronary atherosclerosis
and possible association with platelet aggregation.
c. Emboli from left sided mural thrombi, vegetative
endocarditis, or paradoxic emboli from the right side of heart
through a patent foramen ovale.
Subendocardial infarct - multifocal areas of necrosis or
circumferential necrosis confined to the inner 1/3-1/2 of the
LV wall. May be caused by hypotension, global ischemia,
etc. and does not follow distribution of a single vessel.
1. Key Events in MI
Seconds Onset of ATP depletion
<2 minutes Loss of contractility
20-40 minutes Irreversible cell injury
> 1 hour Microvascular injury
2. Morphology of MI
Time Gross Features Microscopic Features
None EM only relaxation of
myofibrils; glycogen loss;
½ - 4 hours
None Waviness of fibers
4-12 hours Dark mottling Edema, hemorrhage, early
12-24 Dark mottling Coagulative necrosis,
pyknosis, contraction bands
in reperfusion injury
1-3 days Mottling with yellow
necrosis with loss of nuclei
and striations; interstitial
3-7 days Hyperemic border,
phagocytosis of dead
myocytes at border
7-10 days Maximally yellow
and soft, depressed
Phagocytosis of dead cells;
early granulation tissue
10-14 days Red-gray depressed
Granulation tissue with new
vessels and collagen
2-8 weeks Gray-white scar,
border to center of
Increased collagen and
decreased cellularity and
>2 months Scarring complete Dense collagenous scar
3. Complications of MI
a. none (10-20%), death (7-13% of those receiving
aggressive reperfusion therapy)
b. arrhythmias and conduction defects (75-95%)
c. congestive heart failure, pulmonary edema (60%)
d. cardiogenic shock (10-15%)
e. pericarditis (50%)
f. mural thrombosis (40%) and thromboembolism (15%)
g. rupture of ventricle, papillary muscle or ventricular
aneurysm formation (4-8%)
rupture usually occurs at 3-7 days
4. Therapeutic modalities
a. Infarct modification by thrombolysis
b. PTCA - balloon dilatation
c. Directional atherectomy
d. Coronary bypass surgery
e. Coronary artery stents
5. Reperfusion modification of infarction
<20 minutes get salvage of myocardium, may have stunning
2-4 hours get partial salvage with central necrosis
> 6 hours of no benefit in reducing infarct size
Gross findings show hemorrhage in infarcted and
Microscopic shows contraction bands and interstitial RBCs.
D. Chronic IHD with heart failure, hypertrophy and interstitial fibrosis
(ischemic cardiomyopathy). These patients make up 50% of heart
Gross - LV usually dilated, moderate-severe
atherosclerosis, focal small scars confined to the LV wall,
pericardial fibrous adhesions
Microscopic - myocyte hypertrophy and focal atrophy with
myocytolysis of single and clusters of cells; focal small
interstitial scars; coronary atherosclerosis
2. Clinical significance
Slow, progressive heart failure with or without previous MI or
angina, sometimes referred to as ischemic cardiomyopathy
Responsible for 40% of the mortality in IHD
IV. Diagnostic laboratory testing in acute MI
A. Serum enzymes - leak from necrotic cells, there is a more rapid
rise with reperfusion treatment
1. Creatine kinase (CK, CPK) - composed of two subunits "M"
and "B" which combine to yield three isoenzymes MM, MB,
Tissue BB MB MM
Skeletal muscle 0% 2% 98%
Myocardium 0% 15-40% 60-85%
Brain 90% 0% 10%
Bladder 95% 0% 5%
Bowel 100% 0% 0%
CK-MB begins to rise in 2-4 hours, peaks at 24 hours and
returns to normal by 72 hours.
2. Troponin - cardiac muscle specific enzymes, Troponin I and
Troponin T appear within 2-4 hours, peak at 48 hours and
remain elevated 7-10 days. Normally there is no troponin in
3. Aspartate aminotransferase (AST, SGOT) - found in the
cytoplasm and mitochondria of a variety of tissues including
liver, heart, and skeletal muscle
4. Lactate dehydrogenase (LD, LDH) - composed of four
subunits of two different types "H" and "M," and yields five
LD-l (HHHH) 19-39% Myocardium, erythrocytes, kidney
LD-2 (HHHM) 25-50% Erythrocytes, kidney
LD-3 (HHMM) 16-31% Lung
LD-4 (HMMM) 2 - 9% Skeletal muscle
LD-5 (MMMM) 2 -17% Liver, skeletal muscle
LD-2 (most abundant), LD-l, LD-3, LD-4, LD-5 (least abundant)
LD-l/LD-2 < 1 (normally)
V. C-reactive protein (CRP) may predict the risk of MI in patients with
angina. A highly sensitive CRP of >3 mg/L is associated with high risk of
VI. Hyperhomocysteinemia - independent risk factor for vascular disease
including coronary artery disease. Patients with an inborn error of
metabolism causing homocystinuria have premature atherosclerosis.
Other patients may have increased homocysteine due to decreased folate
and B6 intake.
A. Homocysteine plasma levels are increased by 15-40% in patients
with CAD (levels >100 micromols/L). Normal <16 micromol/L.
B. Treated with folic acid, pyridoxine or vitamin B12
VII. BNP – Brain natriuretic peptide (B-type natriuretic peptide) marker
A. Neurohormone predominately produced in the left ventricle in
response to pressure and volume expansion. Synthesis and
secretion is a protective response that is up regulated in patients
with heart failure, resulting in vasodilation and diuresis/natriuresis.
Elevated BNP are seen in hypertension, tachycardia,
cardiomyopathy, MI, mitral and aortic stenosis.
B. Clinical utility
Detect asymptomatic CHF
Objectively assess heart failure severity – correlating with NYHA
Monitor therapy and disease progression
Predict 30-day and 10-month mortality after AMI
C. BNP < 100 pg/ml – no heart failure
BNP 100-300 pg/ml – heart failure is present
BNP 300-600 pg/ml – mild heart failure
BNP 600-1000 pg/ml – moderate heart failure
BNP >1000 pg/ml – severe heart failure
Pathology 6020 - Year 2005
Paul Urie, M.D., Ph.D.
Dec. 12, Monday 10-11 am
ANEURYSMS, VASCULITIS, PERICARDIAL DISEASE AND TUMORS
Reading: Robins Pathologic Basis of Disease 7th
edition: pages 530-553 and
610-615; or in the 6th
edition pages 515-540 and 589-591.
Site of involvement - abdominal aorta, common iliac arteries or
arch and descending thoracic aorta
Clinical significance - rupture, impingement of adjacent structure,
occlusion of a vessel, embolism, abdominal mass
B. Syphilitic aneurysms
Site of involvement - thoracic aorta and arch
Morphology - saccular, fusiform, and cylindroid types with
destruction of the media. Obliterative endarteritis of the vasa
vasorum by lymphocytes and plasma cells causing ischemic injury
to the media with intimal and subintimal scarring. Aortic valve ring
dilatation and insufficiency causing volume overload hypertrophy,
C. Mycotic aneurysm - infection of major artery which weakens the
II. Aortic dissections
This is most common in 40-60 year olds related to hypertension (90%).
Also seen in Marfan’s Syndrome as an abnormality of fibrillin or as an
iatrogenic disorder (catheterization).
Site of involvement - ascending aorta and aortic arch
Morphology - intimal tear with hematoma within media
Cystic medial necrosis - focal separation of the elastic and smooth muscle
of the media by ground substance of connective tissue with
accompanying focal fibrosis of media.
Clinical significance - external hemorrhage and occlusion of arteries.
Type A involves ascending aorta and Type B does not.
A. Classification based on vessel size
1. Large vessel
a. Giant cell arteritis
b. Takayasu’s arteritis
2. Medium-sized vessel
a. Polyarteritis nodosa (PAN)
b. Kawasaki disease
3. Small vessel
a. Wegner’s granulomatosis
b. Churg-Strauss syndrome
c. Microscopic polyangiitis
d. Henoch-Schönlein purpura
e. Essential cryoglobulinemic vasculitis
f. Cutaneous leukocytoclastic angiitis
B. Classification based on pathogenesis
1. Infectious - bacterial, fungal, and viral
a. Immune complex mediated - Henoch-Schönlein, SLE
b. Direct antibody mediated - Kawasaki disease
c. ANCA associated - Wegner’s granulomatosis
d. Cell-mediated - Allograft organ rejection
a. Giant cell arteritis
b. Takayasu’s arteritis
c. Polyarteritis nodosa
C. Polyarteritis nodosa (PAN)
Immune mediated disorder, associated with Chronic Hepatitis B in
30% of patients. There is no association with ANCA.
Site of involvement - kidneys 85%, heart 75%, liver 65%, GI 50%
Medium sized muscular arteries affected by segmental and
transmural lesions usually at branch points
Morphology of lesions (varying ages)
Acute - fibrinoid necrosis and transmural neutrophil,
mononuclear, and eosinophil infiltrate, +/- thrombosis
Healing - fibroblastic proliferation with continued necrosis
Healed - fibrotic thickening, scattered lymphocytes and
plasma cells with calcium deposits
Clinical signs - fever, malaise, weakness, leukocytosis, and
symptoms of specific organ involvement
Treatment – steroids and cyclophosphamide results in 90%
D. Microscopic polyangiitis (leukocytoclastic)
Immune mediated disorder, usually in response to a foreign
antigen, drug, bacteria etc.
It involves small vessels (arterioles, venules and capillaries) of the
skin mucous membranes, lungs, brain, heart, GI tract, kidneys,
and muscle (palpable purpura).
Morphology - fibrinoid necrosis with neutrophil infiltrate, all lesions
are of the same age. Pauci-immune vasculitis means there are little
or no deposits on immunofluorescence.
Diagnosis – skin biopsy
p-ANCA positive in 70% of patients
Treatment is removal of antigenic source
E. Wegener's granulomatosis
Probably a cell-mediated immunity to an inhaled agent; immune
complexes may be seen in the vessels in some patients. M>F; age
Site of involvement - acute necrotizing or granulomatous vasculitis
of the upper and lower respiratory tract, and renal disease with
necrotizing glomerulonephritis present in small arteries and veins
Morphology - focal acute necrosis surrounded by a zone of
fibroblastic proliferation with giant cells and leukocyte infiltrate.
c-ANCA present in 95% of patients with active disease
Treatment is immunosuppression
F. Giant cell (temporal) arteritis
T-cell mediated, antigen driven immune response is most likely
cause. It is the most common of the vasculitides; often have very
high erythrocyte sedimentation rate.
Site of involvement - focal granulomatous inflammation of arteries
of large to small size that affects cranial vessels in older
Morphology – patchy granulomatous lesions with giant cells and
fragmentation of elastic fibers, fibrosis results in nodular thickening
Diagnosis – arterial biopsy (2-3 cm length)
Treatment – high dose steroids
Clinical significance - Involvement of ophthalmic arteries may lead
to blindness and aortic involvement can lead to aneurysm
G. Raynaud’s disease - paroxysmal pallor or cyanosis of digits of
hands or feet due to intense vasospasm without organic changes.
H. Raynaud’s phenomenon - arterial insufficiency of extremities
secondary to arterial narrowing induced by various diseases.
A. Varicose veins
Site of involvement - superficial veins of lower extremities
Clinical significance - stasis dermatitis and ulcers, NOT embolism
B. Phlebothrombosis and thrombophlebitis
Site of involvement - deep leg veins
Clinical significance - pulmonary embolism
Variants - Phlegmasia alba dolens - painful white leg due to
venous inflammation compressing the lymphatics
Migratory thrombophlebitis - migrating venous thrombi
A. Acute lymphangitis
B. Obstructive lymphedema - tumors, surgery, radiation or fibrosis
V. Pericardial Effusion - normally 30-50 ml in pericardial sac
A. Serous - straw-colored or clear watery fluid from congestive heart
failure or hypoproteinemia or scleroderma
B. Serosanguineous - blood-tinged watery fluid from blunt chest
trauma, cardiopulmonary resuscitation, metastatic tumor or
C. Chylous - watery fluid with lipid droplets due to lymphatic
obstruction from either benign or malignant mediastinal tumors
D. Hemopericardium - accumulation of pure blood in pericardial sac;
usually due to traumatic perforation of heart wall, rupture
secondary to acute MI, rupture of intrapericardial aortic aneurysm,
or rarely bleeding diatheses - leukemia or thrombocytopenia
Cardiac tamponade (reduce diastolic filling) may occur with rapid
accumulation of 200-300 ml
VI. Pericarditis - inflammation of the pericardium
1. Infectious agents
a. Viral - Coxsackie, ECHO, influenza, adenovirus or
c. M. tuberculosis or fungal
Rheumatic fever, SLE, Scleroderma, postcardiotomy, or drugs
3. Miscellaneous - MI, uremia, neoplasia, trauma, radiation
B. Acute pericarditis
1. Serous pericarditis
a. Etiology - virus, rheumatic fever, SLE, scleroderma,
tumors, or uremia.
b. Morphology - 50-200 ml exudate with scant numbers
of neutrophils, lymphocytes, and histiocytes and rare
development of fibrous adhesions or organization.
2. Fibrinous or serofibrinous pericarditis
a. Etiology - MI, uremia, radiation, trauma, SLE, viral,
bacterial, or cardiac surgery.
b. Morphology - serous fluid with fibrin, inflammatory
cells, and red cells. Fibrous organization with
adhesive pericarditis rarely restricting cardiac motion.
c. Symptoms and signs - pain, fever, and pericardial
3. Purulent or suppurative pericarditis
a. Etiology - bacterial, mycotic, or parasitic from direct
invasion, hematogenous seeding, lymphatic seeding
or direct introduction.
b. Morphology - thin to creamy pus, 400-500 ml in
volume with reddened, granular coated serosal
Organization is the usual outcome with constrictive
4. Hemorrhagic pericarditis - blood mixed with fibrinous
a. Etiology - M. tuberculosis, neoplasms, or bacterial
b. Morphology - resolution or organization with or
5. Caseous pericarditis - TB and the most frequent cause of
fibrocalcific, chronic constrictive pericarditis.
C. Healed pericarditis
1. Little clinical significance
a. "Soldier's plaque" - thickened non-adherent
b. diffuse or focal obliterative pericarditis
2. Serious clinical importance
a. Adhesive mediastinopericarditis - consequence of
caseous or suppurative pericarditis or previous
cardiac surgery with obliteration of the pericardial sac
and adherence to the surrounding structures.
Increased cardiac work with systolic retractions of rib
cage and pulsus paradoxus.
b. Constrictive pericarditis - dense fibrous or fibrocalcific
scar that limits diastolic expansion and restricts
Small quiet heart with reduced pressure and cardiac
output without hypertrophy or dilatation.
May be a consequence of tuberculous pericarditis.
VII. Cardiac tumors
A. Primary cardiac tumors
Incidence - 0.0017-0.33%
a. Site of involvement - 90% in atria with 4:1 left to right ratio
and covered by endothelium.
b. Morphology - Stellate or globular myxoma cells,
macrophages, and smooth muscle in acid
mucopolysaccharide ground substance. Neoplasm derived
from primitive mesenchymal cells.
c. Clinical significance - "wrecking ball," ball-valve
obstructions, or embolism.
B. Secondary tumors - more commonly involving pericardium than
myocardium. Blood or lymphatic-borne metastasis from carcinomas
or malignant lymphomas.
Adults (>16 years) Children (1-15) Infants (<l year)
Myxoma Rhabdomyoma Rhabdomyoma
Lipoma Fibroma Teratoma
Papillary fibroelastoma Myxoma Fibroma
Angiosarcoma Malignant Teratoma Fibrosarcoma
Rhabdomyosarcoma Rhabdomyosarcoma Rhabdomyosarcoma
VIII. VASCULAR TUMORS
A. Classification of Tumors of Blood Vessels
b. Vascular ectasias
b. Kaposi’s sarcoma
B. Hemangioma - most common vascular tumor, usually in infancy or
childhood; usually small; most often seen on skin but can occur in
Capillary or cavernous subtypes composed of clusters of
endothelial lined spaces filled with RBCs.
C. Kaposi’s sarcoma - associated with AIDS or transplantation; occurs
in the setting of human herpesvirus 8 infection; can be seen on
skin or in visceral organs.
Spindle cell neoplasm with many slit-like vascular channels.
D. Angiosarcoma - highly malignant, bulky tumor. Morphology varies
CONGENITAL HEART DISEASE LAB
HSEB 4300 Teaching Laboratory
December 15 2005 Thursday
History: A 2870 gm baby is born at 37 weeks gestation to a 23 year old
primagravida. The pregnancy was uncomplicated, and no ultrasound was
performed during gestation. The baby initially does well, but then approximately
12 hours following delivery develops respiratory difficulty. The baby has a poor
color, weak pulses, and oxygen saturation of only 90%.
Examine the gross specimen and slide 1.1. What are the findings?
What is the diagnosis?
What is the outcome?
History: Before the era of cardiac surgery, a 10 year old girl lived with her
parents in the highlands above Butte, Montana. She was only half the size of
her 4th grade classmates, and she did not go out to play at recess because she
tired easily. Her skin always had an ashen grey to pale bluish tint.
Examine the gross specimen from a similar case. What are the findings?
What is the diagnosis:
Explain the pathophysiology of this condition, and why was the child eventually
sent to live with relatives in Florida?
History: At 18 weeks gestation, an ultrasound reveals a cardiac defect, along
with a “double bubble” sign suggesting duodenal atresia. Maternal serum alpha-
fetoprotein is low and the beta-HCG is high. The parents elect to proceed with
the pregnancy. The baby is born at 36 weeks. A systolic murmur is present.
Examine the gross specimen and slides 3.1 and 3.2. What are the findings?
Dr. Leonard (a clinical geneticist) is asked to see the baby. She points out the
features seen in slide 3.3. What do you see?
What additional test would help to diagnose the baby’s underlying condition?
What happens if this lesion is not repaired?
History: A 15 year old male is noted on physical examination to have more
development of his upper body than lower body. Physical examination reveals
bounding 4+ radial pulses, but weak 1+ dorsalis pedis pulses. A chest
radiograph reveals clear lung fields, normal cardiac shadow, and rib notching.
What is the abnormality seen in slides 4.1 and 4.2 from other patients with a
Describe the pathophysiology of this condition.
History: A 65 year old male develops increasing orthopnea and exercise
intolerance over the past year. A chest radiograph reveals pulmonary edema
and congestion. The left heart shadow is increased, particularly the left
Compare the lesions seen in slides 5.1 and 5.2. What is present?
What are these conditions?
History: A neonate born at term develops cyanosis within the first day of life. A
systolic murmur is audible on auscultation. Arterial oxygen saturation is only
Examine the gross specimen. What are the findings?
What is the diagnosis:
Explain the pathophysiology of this condition:
PATHOLOGY 6020 YEAR 2005
CONGENITAL HEART DISEASE
Directed Study Handout
Laboratory Session: December 15
10:00-12:00 HSEB 4300
Pathology of Congenital Heart Disease
Acyanotic Cardiac Malformation:
1. Ventricular Septal Defects (“VSD”)
Defects in the ventricular septum may be single (90%) or multiple, they
may be located in the membranous septum (90%), the muscular septum,
or in the conus (subpulmonic).
How does the presence of a VSD alter the hemodynamics? (Hint: What
happens to the pulmonary vascular resistance (PVR) and systemic
vascular resistance (SVR) after birth?)
2. Patent Ductus Arteriosus (“PDA”)
Why does the ductus stay open in the fetus and close immediately after
How does a PDA alter hemodynamics? (Hint: How does aortic pressure
compare to pulmonary artery pressure?)
3. Atrial Septal Defects (“ASD”)
Defects in the atrial septum are usually (90%) at the foramen ovale
(ostium secundum) or in the lowermost portion of the atrial septum
How does an atrial septal defect alter hemodynamics? (Hint: What
happens to left ventricular (LV) compliance and right ventricular (RV)
compliance after birth?)
4. Atrioventricular Septal Defect (“A-V septal defect”, “A-V canal”,
“Endocardial Cushion Defect”)
An ostium primum defect plus a VSD in combination makes a large,
continuous defect. The mitral and tricuspid valves are joined together as
one common A-V valve which crosses the ventricular septum.
Hemodynamically, it acts like a large ASD plus a large VSD.
This is the most common cardiac malformation found in Down syndrome
Acyanotic Obstructive Cardiac Malformations
1. Aortic Stenosis (“AS”)
There are three levels of obstruction:
1) Valvular: Bicuspid, unicuspid, or tricuspid leaflets
2) Subvalvular: Fibrous ring, fibromuscular, or muscular (e.g., Idiopathic
Hypertrophic Subaortic Stenosis, or “IHSS”)
3) Supravalvular: Hour glass, fibrous ring, or hypoplastic segment. This
can be found in William’s Syndrome.
What are the hemodynamic-anatomic consequences of left ventricular
2. Pulmonic Stenosis (“PS”)
There are three levels:
1) Valvular: Bicuspid, unicuspid, tricuspid, dysplastic
2) Subvalvular or infundibular (muscular) is frequently secondary to
valvular, most commonly with tetralogy of Fallot.
3) Supravalvular: Usually seen with tetralogy of Fallot, William’s
Syndrome, or congenital rubella syndrome.
What are the hemodynamic-anatomic consequences of right ventricular (“RV”)
3. Coarctation of the Aorta
Typically, discrete constriction of the aorta just distal to the origin of the
left subclavian artery. Other types: tubular hypoplasia, preductal, and
Collateral circulation from the arch vessels and thoracic arteries supplies
the descending aorta.
What is the role of the PDA in hemodynamic alterations and
manifestations of coarctation?
The metamorphosis of coarctation is shown at the right: (A) fetal
prototype with no flow obstruction, (B) late gestation, aortic ventricle
increases output, antegrade aortic flow bypass via ductal orifice, (C)
neonate, increasing antegrade arch flow, (D) Mature juxtaductal stenosis,
(E) Infantile type, fetal prototype persists
Cyanotic Cardiac Malformations with Decreased Pulmonary Flow
Flow from the right ventricle to the lungs is obstructed so that some desaturated
blood bypasses the lungs and enters the aorta either through intracardiac
defects or aortico-pulmonary communication.
1. Tetralogy of Fallot (“T of F” or “Tet”)
Dr. Fallot described four features:
a. VSD (large, nonrestrictive, perimembranous)
b. Pulmonic stenosis (“PS”) (mild to severe to atresia)
c. RV hypertrophy (“RVH”)
d. Overriding aorta (aorta overrides the VSD)
How does the severity of PS with tetralogy of Fallot affect
Why is there right-to-left shunting?
2. Pulmonic Atresia-Hypoplastic RV
This is a syndrome of tricuspid valve and RV hypoplasia, atresia of the
pulmonic valve, and intact ventricular septum (“IVS”)
What happens to blood which enters the RV? How does blood get from
the vena cavae to the lungs? (Remember there is total obstruction to RV
ejection into the pulmonary artery).
Cyanotic Cardiac Malformations with Increased Pulmonary Flow
1. Transposition of Great Arteries (“TGA”)
Aorta arises from RV and PA arises from LV. Right and left heart
circulations are in parallel. There is no mixing of saturated and
desaturated blood unless there is a VSD, PDA, or ASD.
TGA usually occurs with intact ventricular septum (“IVS”).
TGA may be associated with a VSD, PS, or both.
If there is no mixing, what palliative procedures can be utilized to allow
adequate mixing? How can we create communications between the right
and left hearts?
2. Truncus Arteriosus
Failure of development of the spiral septum results in persistence of the
truncus and absence of part of the conus musculature. This causes a
VSD with overriding trunk from which the pulmonary trunk arises.
Hemodynamically, this situation is similar to a large VSD and PDA, but
both ventricles empty into the truncus so there is admixture of ejected
3. Hypoplastic Left Heart Syndrome
There is usually severe hypoplasia of LV, mitral valve, ascending aorta,
and aortic valvular atresia. Blood from RV is ejected into the PA and
passes through the lungs as well as through the PDA into the descending
aorta, and retrograde into the aortic arch and descending aorta.
How does pulmonary venous blood returning to the left atrium get to the
Why do these newborns die within days after birth?
When a cardiac malformation, such as a large ASD or VSD, with a left-to-
right shunt, has been present for a long time, there can be reversal of the
shunt. This occurs because of the increased pulmonary blood flow that
produces increasing pulmonary hypertension.
Answer to congenital heart disease questions:
How does the presence of a VSD alter the hemodynamics? (Hint: What
happens to the pulmonary vascular resistance (PVR) and systemic vascular
resistance (SVR) after birth?)
At birth, there is relatively high pulmonary vascular resistance.
Resistance drops as the pulmonary circulation assumes a more adult
configuration. This causes decreased pressures on the right, so that there
is shunting of oxygenated blood from left to right. The larger the shunt,
the greater the workload for the left ventricle and the more likely
congestive heart failure will occur. Over time, the increased flow to the
right results in increasing pulmonary vascular resistance (pulmonary
Why does the ductus stay open in the fetus and close immediately after birth?
In fetal life, the pulmonary vascular resistance is high and blood from the
pulmonary artery is shunted via the ductus into the aorta. After birth, pulmonary
pressures drop and there is no longer the right to left shunt, and the ductus
How does a PDA alter hemodynamics? (Hint: How does aortic pressure compare to
pulmonary artery pressure?)
Aortic pressure is higher than pulmonary arterial pressure, so that a PDA
creates a left to right shunt.
How does an atrial septal defect (ASD) alter hemodynamics? (Hint: What happens to
left ventricular (LV) compliance and right ventricular (RV) compliance after birth?)
An ASD creates a left to right shunt following birth because the left-sided
pressures are higher than the right. However, the pressure differential across an
ASD is lower than that for a VSD, because atrial pressures are lower.
What are the hemodynamic-anatomic consequences of left ventricular (“LV”)
LV outflow obstruction leads to increased workload on the left ventricle, resulting
in LV hypertrophy, then dilation. The same situation exists with systemic
hypertension. When the LV fails, the left-sided failure causes pulmonary edema.
What are the hemodynamic-anatomic consequences of right ventricular (“RV”)
RV outflow obstruction leads to increased workload on the right ventricle,
resulting in RV hypertrophy, then dilatation. The same situation exists when the
pulmonary vascular bed is decreased with pulmonary diseases such as
pulmonary emphysema or pulmonary fibrosis, leading to cor pulmonale. When
the RV fails, the right-sided failure leads to hepatic passive congestion,
peripheral edema, and body cavity effusions.
What is the role of the PDA in hemodynamic alterations and manifestations of
The presence of a PDA with the coarctation makes a difference. A pre-
ductal coarctation along with a PDA means that unoxygenated blood can
be shunted to the aorta. A post-ductal coarctation with a PDA can create
a left to right shunt. If no PDA is present, the symptoms may not be
severe, and the condition is diagnosed by relative hypertension in upper
extremities compared to lower extremities.
How does the severity of pulmonic stenosis (PS) with tetralogy of Fallot affect
The greater the outflow obstruction, the greater the load on the right
ventricle and the greater the right to left shunt. If the amount of PS is
minimal, then there may in fact be a left to right shunt across the VSD.
Why is there right-to-left shunting with tetralogy of Fallot?
If the degree of pulmonic obstruction is moderate to severe, then the
pressure exceeds that of the left ventricle, leading to a right to left shunt
across the VSD and cyanosis from mixing of unoxygenated blood.
With pulmonic atresia, what happens to blood which enters the RV? How does
blood get from the vena cavae to the lungs? (Remember there is total
obstruction to RV ejection into the pulmonary artery).
Blood has to shunt via an ASD (foramen ovale remains patent) and a
In transposition of the great arteries (TGA), if there is no mixing, what palliative
procedures can be utilized to allow adequate mixing? How can we create
communications between the right and left hearts?
Create a surgical ASD or VSD.
With a hypoplastic left heart, how does pulmonary venous blood returning to the
left atrium get to the RV?
A PDA is essentially the only connection
Why do newborns with hypoplastic left heart die within days after birth?
There is not enough systemic cardiac output to sustain life in many
cases. The severity depends upon the degree of hypoplasia. The baby
may survive for variable periods of time. There may be time to
consider options such as repair (Norwood procedure) or